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Synthesis of New Acyclic Pyrimidine Nucleoside Analogues and Preliminary of Their Cytotoxic and Genotoxic Effects In Vitro


Osmanović, Amar; Salihović, Mirsada; Kopjar, Nevenka; Želježić, Davor; Roca, Sunčica; Špirtović-Halilović, Selma; Šapčanin, Aida; Završnik, Davorka
Synthesis of New Acyclic Pyrimidine Nucleoside Analogues and Preliminary of Their Cytotoxic and Genotoxic Effects In Vitro // Research journal of pharmaceutical, biological and chemical sciences, 10 (2019), 1; 493-502 (međunarodna recenzija, članak, znanstveni)


Naslov
Synthesis of New Acyclic Pyrimidine Nucleoside Analogues and Preliminary of Their Cytotoxic and Genotoxic Effects In Vitro

Autori
Osmanović, Amar ; Salihović, Mirsada ; Kopjar, Nevenka ; Želježić, Davor ; Roca, Sunčica ; Špirtović-Halilović, Selma ; Šapčanin, Aida ; Završnik, Davorka

Izvornik
Research journal of pharmaceutical, biological and chemical sciences (0975-8585) 10 (2019), 1; 493-502

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Pyrimidine analogues ; Acyclic nucleosides ; CBMN assay ; Genotoxicity ; Cytotoxicity

Sažetak
Nucleoside analogues represent an important class of compounds of wide application range in antiviral and antitumor therapy. A regular procedure in early phases of new drugs development includes assessment of cytotoxicity and genotoxicity (mutagenicity). Here we report the synthesis of two novel C-5 hydroxypropyl pyrimidine nucleosides bearing side chains like those present in drugs already used in therapy (penciclovir and cidofovir). To confirm structures of the newly synthesized compounds FT-IR, HPLC-MS and NMR spectroscopy in solution were used. New hydroxypropyl pyrimidine nucleosides were N-3-(2, 3-dihydroxypropyl)-5- (3-hydroxypropyl)pyrimidine-2, 4-dione and N-3- (4-hydroxy-3-(hydroxymethyl)butyl)-5-(3- hydroxypropyl)pyrimidine-2, 4-dione.Along with two new, we have also tested three previously synthesized nucleosides for genotoxicity and cytotoxicity using cytokinesis-block micronucleus (CBMN) assay on human peripheral blood lymphocytes. Not many studies so far used the same cell model and CBMN assay to determine cyto-/genotoxicity of pyrimidine nucleosides. Results of CBMN assay did not indicate statistically significant cyto-/genotoxicity towards human peripheral blood lymphocytes. Since preliminary testing did not suggest significant genotoxic or cytotoxic potency of novel hydroxypropyl pyrimidine nucleosides, they are excellent candidates for further biological evaluation, primarily as antiviral agents.

Izvorni jezik
Engleski

Znanstvena područja
Kemija



POVEZANOST RADA


Ustanove
Institut za medicinska istraživanja i medicinu rada, Zagreb,
Institut "Ruđer Bošković", Zagreb

Časopis indeksira:


  • Web of Science Core Collection (WoSCC)
    • Emerging Sources Citation Index (ESCI)